Actinobacillus actinomycetemcomitans is a non-motile, gram-negative facultative coccobacillus which colonizes the human oral cavity and upper respiratory tract. Overwhelming microbial, immunological and clinical evidence implicates A. actinomycetemcomitans in the pathogenesis of localized juvenile periodontitis and cases of rapid and refractory periodontal disease. This pathogen has been associated with other serious human infections such as endocarditis, soft tissue abscesses, and more recently cardiovascular disease. The periodontium has been implicated as the reservoir of these extraoral infections, although little is known about the mechanisms this pathogen utilizes to infiltrate and disseminate in tissues. The invasion into epithelial cells in vitro is well established and this periodontopathogen has been localized inside epithelial cells and found in sub epithelial cell layers in tissue biopsy from infected individuals. Our laboratory has demonstrated that A. actinomycetemcomitans utilizes microtubules for intracellular trafficking and exit from epithelial cells. The data suggest that microtubules play a critical role in the spread and movement of A. actinomycetemcomitans and provide the first evidence that host cell dispersion of an intracellular pathogen may involve the usurpation ofmicrotubules. To further understand this unique interaction, we propose to 1) identify and characterize the bacterial macromolecule(s) that are involved in the interaction with microtubules and 2) characterize the component(s) of the epithelial cell microtubule asters that interact with A. actinomycetemcomitans. The identification of these components will be important in understanding the processes that this pathogen uses to survive in the oral cavity and disperse into deeper tissues.